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M Saunders

Publications and source records attributed to M Saunders.

At least 19 recordsLinked to original sources
PubMed2006

Cost-effectiveness of oxaliplatin and capecitabine in the adjuvant treatment of stage III colon cancer.

For many years, the standard treatment for stage III colon cancer has been surgical resection followed by 5-fluorouracil in combination with folinic acid (5-FU/LV). Ongoing clinical trial evidence suggests that capecitabine and oxaliplatin (in combination with 5-FU/LV) may improve disease-free survival and overall survival when compared against 5-FU/LV alone in the adjuvant setting. This study evaluates the cost-effectiveness profiles of these two regimens in comparison to standard chemotherapy, using evidence from two international randomised controlled trials. Survival modelling techniques were employed to extrapolate survival curves from the two trials in order to estimate the long-term benefits of alternative treatment options over the remaining lifetime of patients. The health economic analysis suggests that capecitabine is expected to produce greater health gains at a lower cost than 5-FU/LV. Oxaliplatin in combination with 5-FU/LV is estimated to cost pounds 2970 per additional QALY gained when compared to 5-FU/LV alone. Future research should attempt to elucidate uncertainties concerning the optimal roles of capecitabine and/or oxaliplatin in the adjuvant setting in order to achieve the maximum level of clinical benefit.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Management of advanced colorectal cancer: state of the art.

Colorectal cancer (CRC) caused over 500 000 deaths worldwide in 2002. Recent advances in the treatment of advanced disease include the incorporation of two new cytotoxic agents, irinotecan and oxaliplatin, into first-line regimens. The concept of planned sequential therapy involving three active agents during the course of a patient's treatment is evolving. Coupled with the integrated use of targeted monoclonal antibodies, we can now expect overall survival rates for advanced disease to exceed 20 months. This review considers current treatments and suggests where future progress may occur.

Antineoplastic Agents↗
PubMed2006

Fitness of hybrids between rapeseed (Brassica napus) and wild Brassica rapa in natural habitats.

Fitness of hybrids between genetically modified (GM) crops and wild relatives influences the likelihood of ecological harm. We measured fitness components in spontaneous (non-GM) rapeseed x Brassica rapa hybrids in natural populations. The F1 hybrids yielded 46.9% seed output of B. rapa, were 16.9% as effective as males on B. rapa and exhibited increased self-pollination. Assuming 100% GM rapeseed cultivation, we conservatively predict < 7000 second-generation transgenic hybrids annually in the United Kingdom (i.e. approximately 20% of F1 hybrids). Conversely, whilst reduced hybrid fitness improves feasibility of bio-containment, stage projection matrices suggests broad scope for some transgenes to offset this effect by enhancing fitness.

Brassica napus↗
PubMed2005

Impact of laparotomy and liver resection on the peritoneal concentrations of fibroblast growth factor 2, vascular endothelial growth factor and hepatocyte growth factor.

PURPOSE: Some data have suggested that major surgery is associated with the post-operative growth of residual tumour masses but the mechanism of this is unknown. This study was designed to determine the relationship between intraperitoneal (IP) cytokine levels, and laparotomy in benign and malignant settings. METHODS: Intraperitoneal fluid specimens were obtained at the start and at the end of laparotomy in patients with benign conditions (n=10) and in others undergoing resection of hepatic metastases from colorectal cancer (n=10). Using ELISA the concentration of the angiogenic cytokines, HGF, VEGF-A, VEGF-C, VEGF-D and FGF-2 was determined. RESULTS: The data show that in 16 of 20 patients there was a significant increase (P=0.006) in the IP concentration of hepatocyte growth factor (HGF) but not in the other growth factors by the end of the operation. The mean increase in HGF concentration was 821.5 pg/ml (95% CI: 11.0-6,426.0). Neither the groups (malignant and non-malignant) nor the length of operation correlated with greater or lesser increases in HGF. CONCLUSION: The observation that the increase in HGF occurred in both the cancer and non-cancer groups suggests that it is the surgery rather than the disease that is associated with the increased cytokine concentration. As HGF is a potent endothelial, epithelial and mesenchymal mitogen the data highlight HGF as a potential target for anti-cancer treatments in the peri-operative period. However, investigators should closely monitor wound healing as this may be compromised by this new class of drugs.

Ascitic Fluid↗
PubMed2005

Association between polymorphisms of the GPX1 gene and second primary tumours after index squamous cell cancer of the head and neck.

We investigated the association between genetic polymorphisms in GPX1 gene amongst patients who had index squamous cell carcinoma (SCCHN) and a second primary tumour (SPT) after a primary SCCHN in a case-control study. GPX1 genotypes were determined for 61 patients with SPT and for 259 control subjects by a PCR technique using a fluorescent-labelled primer. Analysis was by an ABI automated fluorescent sequencer. The associations between specific genotypes and the development of SPT were examined by logistic regression. A significant difference was found between the control group and the SPT cases in allele frequencies of GPX1 ALA( *)6 and ALA( *)7 (p(trend)=0.04). These results suggest that polymorphisms in the GPX1 gene may be a marker for SPT development and further studies are indicated.

Adult↗
PubMed2005

p73 modulates HIV-1 Tat transcriptional and apoptotic activities in human astrocytes.

HIV-1 Tat is a potent transcriptional activator of the viral promoter with the ability to modulate a number of cellular regulatory circuits including apoptosis. Tat exerts its effects through interaction with viral as well as cellular proteins. Here, we studied the influence of p73, a protein that is implicated in apoptosis and cell cycle control, on Tat apoptotic function in the central nervous system. We recently demonstrated the ability of Tat to associate with p73, and that this association modulates Tat transcriptional activity (Amini et al., Mol Cell Biol 2005; 18: 8126-8138). We demonstrated that p73 interferes with Tat-mediated apoptosis by preventing the up-regulation of Bax and down-regulation of Bcl-2 proteins in astrocytes. Thus, the interplay between Tat and p73 may affect Tat contribution to apoptotic events in the brain, limiting its involvement in the neuropathology often observed in the brains of HIV-1 patients.

Apoptosis↗
PubMed2005

Pre-operative plasma levels of vascular endothelial growth factor A, C and D in patients with colorectal cancer.

AIMS: Vascular endothelial growth factor (VEGF)-C and VEGF-D are angiogenic and lymphangiogenic members of the VEGF family of growth factors. Increased VEGF-C or VEGF-D expression in human tumours may be associated with lymph-node metastasis and lymphatic invasion. Circulating plasma levels of VEGF-A, VEGF-C and VEGF-D were measured in patients with colorectal cancer, and assessed for their usefulness as a diagnostic tool for determining lymph-node metastasis. MATERIALS AND METHODS: One hundred and twenty patients with colorectal cancer and 50 healthy control patients were included in the study. Plasma growth-factor levels were assessed by enzyme-linked immunosorbent assays. RESULTS: No significant differences in plasma VEGF-C or VEGF-D levels were seen between patients subgrouped by clinicopathological variables. In particular, there were no differences in median plasma VEGF-C or VEGF-D level in patients with and without lymph-node involvement (VEGF-C: 11.2 U/ml [range, 4.9-51.9] vs 9.9 U/ml [4.4-93.4 U/ml]; P = 0.90; VEGF-D: 335 pg/ml [113-1102] vs 316.5 pg/ml [0-1343]; P = 0.68). CONCLUSIONS: Circulating plasma levels of VEGF-C and VEGF-D do not allow pre-operative identification of lymph-node status in patients with colorectal cancer.

Adult↗
PubMed2005

Dose implications of fluoroscopy-guided positioning (FGP) for lumbar spine examinations prior to acquiring plain film radiographs.

Fluoroscopy is increasingly being used as a positioning device prior to obtaining plain film radiographs. This is particularly true for those examinations where the type of projection and habitus of the patient present difficulties. An example is the examination of the lumbar spine; especially the L5/S1 projection. The purpose of this study was to determine the effect of fluoroscopy-guided positioning (FGP) on patient dose. The study assessed the difference in dose-area product (DAP) between conventional film-screen radiography (FSR) and a FGP assisted series of the lumbar spine. DAP values were monitored on 102 patients (50 FSR, 52 FGP) over 7 (4 FSR, 3 FGP) study sites. The median values for all FGP and FSR procedures were 8.3 Gy cm(2) and 12.5 Gy cm(2), respectively. The differences in doses were attributed to lower mAs and tighter collimation used in FGP assisted procedures. The study has demonstrated that it is possible to achieve lower DAP values using FGP. What now has to be asked is whether FGP should be acknowledged and further introduced into clinical practice. If so, there is a need for careful monitoring and reporting of dose so that strict protocols can be set in place to ensure the ALARA principle is enforced.

Adult↗
PubMed2004

Blockade of platelet-derived growth factor receptor-beta by CDP860, a humanized, PEGylated di-Fab', leads to fluid accumulation and is associated with increased tumor vascularized volume.

PURPOSE: CDP860 is an engineered Fab' fragment-polyethylene glycol conjugate, which binds to and blocks the activity of the beta-subunit of the platelet-derived growth factor receptor (PDGFR-beta). Studies in animals have suggested that PDGFR-beta inhibition reduces tumor interstitial fluid pressure, and thus increases the uptake of concomitantly administered drugs. The purpose of this study was to determine whether changes in tumor vascular parameters could be detected in humans, and to assess whether CDP860 would be likely to increase the uptake of a concurrently administered small molecule in future studies. PATIENTS AND METHODS: Patients with advanced ovarian or colorectal cancer and good performance status received intravenous infusions of CDP860 on days 0 and 28. Patients had serial dynamic contrast-enhanced magnetic resonance imaging studies to measure changes in tumor vascular parameters. RESULTS: Three of eight patients developed significant ascites, and seven of eight showed evidence of fluid retention. In some patients, the ratio of vascular volume to total tumor volume increased significantly (P < .001) within 24 hours following CDP860 administration, an effect suggestive of recruitment of previously non-functioning vessels. CONCLUSION: These observations suggest that inhibition of PDGFR-beta might improve delivery of a concurrently administered therapy. However, in cancer patients, further exploration of the dosing regimen of CDP860 is required to dissociate adverse effects from beneficial effects. The findings challenge the view that inhibition of PDGF alone is beneficial, and confirm that effects of PDGFR kinase inhibition mediate, to some extent, the fluid retention observed in patients treated with mixed tyrosine kinase inhibitors.

Adult↗
PubMed2003

Using cyanide to put noble gases inside C60.

After fullerenes are heated in the presence of a noble gas or an unreactive molecule at 650 degrees C and 3000 atm pressure, a small fraction of the fullerene molecules contain the atom or molecule. The incorporation fraction is greatly enhanced by adding potassium cyanide to the reaction mixture. The details of the preparation are described here.

Journal Article↗
PubMed2003

The impact of FDG PET on the management of occult primary head and neck tumours.

AIMS: The aim of this study was to investigate the impact of positron-emission tomography (PET) with 18F-labelled fluoro-2-deoxy-D-glucose (FDG) in the management of occult primary head and neck tumours. MATERIALS AND METHODS: We reviewed 16 patients with squamous cell carcinoma (SCC) and one patient with undifferentiated carcinoma of cervical lymph nodes (N1-4; N2a-9; N2b-2; N3-2). All patients had full clinical assessment, including examination under anaesthesia (EUA), with biopsy of all suspicious areas and random biopsies of sites likely to harbour an occult primary site. Nine patients underwent magnetic resonance imaging (MRI) of the head and neck, three underwent computed tomography (CT) and five underwent both CT and MRI. None of these studies were able to locate a primary tumour. Patients received 350 MBq FDG intravenously. Emission transmission scans of the extra-cranial head, neck and thorax were obtained using an ECAT Exact 47 at least 60 min after injection. The images were interpreted by the same radiologist experienced in PET, independent of the final outcome. The influence of FDG PET on management was assessed on review of the patients' notes after treatment or when treatment had been deemed unnecessary. RESULTS: FDG PET suggested a primary site in eight of the 17 patients (tongue base 5; nasopharynx 1; tonsil 1: supraglottis 1). Pathological confirmation was obtained in four patients and one patient died of progressive disease at the primary site. In nine patients, the primary site was not identified on FDG PET. In six of these patients, no primary site was found during follow-up (range 8-36 months: mean 20 months). One patient died before treatment commenced, and there were two histologically confirmed false-negative FDG PET results: one tonsil SCC and one lateral pharyngeal wall SCC. FDG PET affected treatment plans in nine of the 17 (53%) patients in whom a primary site was suggested (altered radiotherapy plan 6; radiotherapy with curative intent to palliative radiotherapy 1; radiotherapy to surgery and post-operative radiotherapy 1), and in one patient where no occult primary was localised (radiotherapy to surgery 1). FDG PET had a sensitivity, specificity, positive and negative predictive value of 62%, 66%, 62% and 62%, respectively.

Aged↗
PubMed2003

Consensus: the follow-up of the treated patient.

This is the first consensus document on the follow-up of the treated patient with non-small cell lung cancer that has been written by this group. The document has been drawn up by doctors coming from many different cultures and philosophical backgrounds. It acknowledges that there are published guidelines on the follow-up particularly those in trials, and does not wish to contradict these. There is lack of evidence-based medicine to recommend a strong general policy in this area. For those patients who were treated with curative intent the initial follow-up will depend upon the toxicity that is evident from the treatment given. Thereafter the interval between follow-up visits should be every 3 months for the first two years, then every 6 months for up to five years. Rapid and easy access to the multidisciplinary team should be available. Full examination and chest X-ray should be carried out on each visit but other investigations should be determined by clinical need. For those patients treated with palliative intent the interval between follow-up visits once the acute reactions have settled will depend upon the adequacy of the control of the symptom and the availability of separate palliative care teams. At all times the patient should have rapid access to the multidisciplinary team and in general frequent follow-up, that is at intervals of one to two months, may be appropriate during the first six months. Follow-up constitutes an important part of lung cancer management. Efforts should be made to gain clinical material to give us evidence-based guidelines.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Use of a mandibular advancement device in obstructive sleep apnoea.

The present study investigated the effectiveness of an intra-oral mandibular advancement device in the treatment of patients with obstructive sleep apnoea (OSA) who could not tolerate or who had failed to comply with continuous positive airway pressure (CPAP). Thirty-five patients diagnosed by sleep study as suffering from OSA, who had either been unable to tolerate or had been non-compliant with CPAP treatment, were included in the study. The subjects completed an Epworth sleep questionnaire. The subjects then had an oral appliance made. After using the appliance for 3 months, the patients repeated the questionnaires and had a repeat sleep study performed with the oral appliance in situ. Thirty-one subjects completed the investigation. Mean AHI pre- and post-study were 26.64 and 24.06, respectively (P > 0.05). Mean Epworth scores pre- and post-study were 16.32 and 14.64, respectively (P > 0.05). Those patients with a pre-study AHI < 20 (n = 23), however, did significantly better with the appliance (P < 0.0001). Those patients with a pre-study AHI > 20 did not benefit from this device (P > 0.05). The main problems encountered were initial jaw discomfort in 18 patients and dry mouth in 11 patients (both of which improved with continued usage). It was concluded that the type of appliance used in this study can be recommended for those with mild OSA who are unable to tolerate CPAP.

Female↗
PubMed2003

Doses to fetal and maternal organs from intravenous 59FeCl3 or 57CoCl2.

Doses from intravenous intakes of 59Fe or 57Co chloride during pregnancy were estimated. Near term fetal organ doses were derived via the MIRDOSE3 newborn phantom, with mean dose/cumulated activity (S) values rescaled for compatibility with near term fetus whole body S. A detailed in vivo biodistribution database provided indications of residence times in important maternal and fetal organs. 59Fe doses to the fetus whole body from early to late pregnancy were 7-11 mGy MBq(-1) (8.5-14.3 mSv MBq(-1)), similar to that to the mother. Doses to near term fetal spleen (59 mGy MBq(-1)), liver (36), and red marrow (9) were similar or higher than to the mother. 57Co doses to fetus whole body from early to late pregnancy were 0.7-3.3 mGy MBq(-1) (2.5-8.2 mSv MBq(-1)), similar or higher than to the mother. Doses to near term fetal small intestine (34 mGy MBq(-1)). liver (4.7) and red marrow (2.7) were similar or higher than to the mother.

Body Burden↗
PubMed2003

Delayed diagnosis of foreign body aspiration in children.

Foreign body aspiration in children is common and usually presents with an initial episode of choking with subsequent respiratory symptoms. There may be cough, wheeze, or stridor, with decreased or abnormal breath sounds on examination. However, it can mimic other illnesses and cause difficulty in diagnosis. Radiological investigations may help to confirm aspiration but should not be used to exclude it. Three cases are presented of foreign body aspiration with a delay in diagnosis ranging from days to weeks. It is believed that delay could have been avoided with a more careful approach to the history and more appropriate use of investigations. These cases demonstrate that children with a history of choking and subsequent symptoms should be referred for bronchoscopy.

Bronchi↗
PubMed2002

Extracranial fasciitis in childhood: a sheep in wolf's clothing.

Soft tissue tumours in children are rare, and the differentiation between pseudosarcomatous tumours and sarcomas is difficult. Rapidly-enlarging masses within the head and neck region in infants require rapid diagnosis and prompt definitive treatment to lessen psychological burden on the parents and the surgical team. We present a case of a 17-month-old girl who had a large, rapidly-enlarging soft tissue mass within the maxilla which was excised. The diagnosis of childhood extracranial fasciitis was confirmed histopathologically. We emphasise the importance of conservative excision once the diagnosis has been confirmed.

Diagnosis, Differential↗